Co-expression of genes with estrogen receptor-alpha and progesterone receptor in human breast carcinoma tissue

Background: To detect genes associated with the expression of ESR1 and PGR - as well as of their protein products, estrogen receptor (ER) and progesterone receptor (PR) - 221 de-identified invasive ductal carcinomas of the breast were investigated. Our long-term goal is to decipher relationships between the expression of ER- and PR-associated genes and breast cancer behavior to improve diagnostics and identify new molecular targets for drug design. Materials and methods: Frozen tissue sections were evaluated for structural integrity and pathology after hematoxylin and eosin staining. ER and PR protein levels were quantified by either enzyme immunoassay or radioligand binding assay. Total RNA preparations were reverse transcribed for qPCR measurements of ESR1, PGR and 31 gene candidates. Results: Both ESR1 and PGR expression levels were correlated with their cognate receptor protein expression (Pearson correlations of 0.82 and 0.68, p <0.001, respectively), to assess molecular relationships between clinically relevant biomarkers in tissue specimens. Coordinate expression of EVL, NAT1, TBC1D9, SCUBE2, RABEP1, SLC39A6, TCEAL1, FUT8, XBP1, PTP4A2 or GATA3 with either ESR1 or PGR was detected. Conclusions: Examination of relationships between ESR1 and PGR gene expression and that of other genes of interest indicated: a high degree of correlation between ESR1 levels and expression of NAT1, SCUBE2, XBP1 and GATA3; and a high degree of correlation between PGR expression and that of NAT1, ESR1, SCUBE2 and RABEP1. These results suggest that direct relationships of these genes exist with estrogen and progestin receptor mediated pathways. Pathway analysis software provided additional evidence of gene interactions.